The purpose of this project is to "rescue" the psychosis-prone brain by normalizing the cognitive dysfunction of adolescents and young adults who are at high risk for developing a first psychotic episode. We will apply 80 hours (16 weeks) of intensive computerized neuroadaptive cognitive training exercises to 40 ultra high-risk (UHR) adolescents and transitional age youth, ages 16-25, who meet diagnostic criteria for the "prodromal syndrome" in schizophrenia. Subjects will be drawn collaboratively from two research sites in California (UCSF and UC Davis). The effects of this neuroplasticity-based cognitive remediation on these very high-risk youth will be compared to the effects obtained in an age- and sex- matched group of healthy comparison subjects, and to the effects obtained in a matched group of 40 UHR youth who undergo a computer games "active control" condition. This approach is supported by data from our current NIMH-funded randomized controlled trial of neuroplasticity-based cognitive remediation in adult patients with chronic schizophrenia, where highly significant improvements in processing speed, working memory, and verbal learning and memory, are apparent after 60 hours of intensive training. Preliminary "open-label" data from three UHR adolescents who participated in 40 hours of training exercises showed mean z-score improvements of 0.9 on attention/working memory, 0.7 on episodic memory, and 1.1 on executive functioning. Our overall aims are thus to: 1) Use principles from experimental neuroscience to harness mechanisms of brain plasticity and correct aberrant information processing in the cortex of UHR individuals; 2) Prevent or attenuate the onset of psychotic disorder and improve adaptive functioning in these adolescents and transitional age youth. PUBLIC HEALTH NARRATIVE: The purpose of this study is to use neuroscience-guided computerized training exercises to remediate the thinking difficulties that occur in young people who are at very high risk of developing a psychotic episode. If this intervention proves useful, it will provide a non- pharmacological treatment approach for young people that is safe and easy to apply, and that may reduce the risk for serious mental illness as well as improve long-term outcome. [unreadable] [unreadable] [unreadable] [unreadable]